monella enterica serovar Typhimurium is a common cause of gastroenteritis. Virulence is determined by five Salmonella Pathogenicity Islands (SPI) encoded on the bacterial chromosome. SPI1 and SPI2 encode the structural components of two Type Three Secretion Sytems (TTSS) that translocate effectors into the host cell. The SPI1 effector SigD is an inositol phosphatase that induces the activation of Akt/PKB a mammalian serine threonine kinase. The role of Akt activation in pathogenesis remains unclear, however, in cultured epithelial cells it appears to be involved in preventing the onset of apoptosis in infected cells. More specifically we have found that a sigD deletion mutant induces Caspase 3 activation compared to wild type. This may be important for the survival and replication of intracellular bacteria. In macrophages activation of Akt by Salmonella is more complex since lipopolysaccharide will activate the kinase in the absence of SigD. Comparison of the two pathways has revealed important differences. In particular, SigD-mediated activation is insensitive to Wortmannin a well described inhibitor of Akt activation via phosphatidylinositol-3-kinase. Thus SigD-dependent Akt activation appears to occur via a novel pathway.